While the knowledge of microbial antigens has permitted the successful development of vaccines against infections, lack of comparable knowledge of human cancer antigens has hampered the development of human cancer vaccines of defined cancer-restricted antigenicity. Recent advances based on autologous serological typing of cultured melanoma cells have led to the identification of two classes of melanoma-restricted cell surface antigens, Class I, detected only on the autologous melanoma cell, and Class II, shared by other melanomas. We propose to test, in a sequential fashion, various types of melanoma vaccines expressing Class I/II antigens to determine conditions for maximal immunogenicity. In initial tests of vaccines prepared from irradiated autologous cultured melanoma cells, antibody to Class I/II antigens was rarely induced or augmented. Therefore, we intend to test vaccines carrying additional antigenic determinants, with the expectation that these determinants will provide "help" for the recognition of Class I/II melanoma antigens. The vaccines will be prepared from (1) irradiated cultured allogeneic melanoma cells expressing cross-reacting melanoma cell surface antigens, (2) irradiated cultured autologous melanoma cells infected with vesicular stomatitis virus, (3) irradiated chemically modified autologous melanoma cells, (4) irradiated intraspecies or interspecies hybrids expressing Class I/II antigens, and (5) immunogenic forms of isolated Class I/II antigens. The relevant immunogenicity of the vaccines will be determined by comprehensive analysis of the patients' antibody response to Class I/II antigens. This is an experimental pilot study concerned with analysis of the serological response to vaccine administration. If a change in serological reactivity to Class I/II melanoma antigens is induced with some regularity, a clinical immunotherapy trial will be designed.